Mutations in the fruitfly, Drosophila melanogaster, will be used to answer the question of whether aging is genetically programmed. We propose to screen ethyl-methanesulfornate-treated X chromosomes and autosomes for three classes of mutations that affect longevity and can be used to probe the basic biology of aging. Three general classes of mutations will be isolated: Class I - ts adult-lethal mutations: We will screen for temperature-sensitive adult-lethal mutations with TSPs in the post-eclosion stages 0-5 days, 6-10 days, and 10 days-on. These mutations will be used to determine if regular program of gene activity exists in adults in which aging could be encoded. In addition, mutations which act only late in the adult stage, after reproductive maturity, will support the notion that aging is a genetically regulated process. Class II - Mutations that delay senescence: Mutations from Class I with late onset TSPs for adut lethality will be used to counterselect mutants which prolong the state of early adulthood. Independently, we will screen for mutations which delay the time of onset of age-dependent loss of geotaxis, phototaxis, flight, or reproduction. Each stock will be inspected for its longevity and for the time of loss of the other characteristics. Class III - Mutations which act during development but influence adult longevity. Ts mutations that prolong the larval lifespan will be isolated and tested for possible independent effects on adult longevity. We shall also screen for ts mutants that interfere with normal programmed cell death in eithe imaginal discs or larval tissues. These will then be tested for independent effects on cell death in aging adults. Lastly we shall screen for ts mutations with TSPs during development but which affect only the adult, causing either premature death, or prolonged adult life. Respectively, those would identify genes which act during development and normally either (1) promote normal longevity, or (2) set a clock which initiates the aging process.